Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


A Study To Evaluate the Effectiveness and Safety of the Interleukin-6 (IL-6) Receptor Antagonist Tocilizumab (TCZ) after 4 and 24 Weeks in Patients with Active Rheumatoid Arthritis (RA)Final Effectiveness Results of the TAMARA Study.

Feist1,  Eugen, Rubbert-Roth2,  Andrea, Braun6,  Jürgen, Kaufmann4,  Jörg, Kellner7,  Herbert L., Kurthen3,  Reiner, Wollenhaupt5,  Jürgen

Campus Charité Mitte, Med. Klinik Abt. Rheumatologie u. Klin. Immunologie, Berlin, Germany
Klinik I für Innere Medizin, Uniklinik Cologne, Cologne, Germany
Praxis für Innere Medizin und Rheumatologie, Aachen, Germany
Praxis für Innere Medizin und Rheumatologie, Ludwigsfelde, Germany
Rheumatologikum Hamburg, Schön-Klinik Hamburg-Eilbeck, Hamburg, Germany
Rheumazentrum Ruhrgebiet, St. Josefs-Krankenhaus, Herne, Germany
Schwerpunktpraxis fuer Rheumatologie und Gastroenterologie, Munich, Germany

TAMARA was a multi-center, open-label, single-arm (TCZ 8 mg/kg iv q4w), Phase IIIb study over 24 weeks (wks) to confirm the effectiveness and safety of TCZ in a treatment setting close to real-life medical care in Germany. Pts. with moderate/severe RA in spite of treatment with conventional (c)DMARDs and/or Biologics were enrolled at 70 sites; inclusion criteria included baseline DAS28 >3.2, ESR >=28mm/h or CRP >=1mg/dL, and previous treatment with at least 1 cDMARD continued during the study. Primary endpoint was the proportion of pts. achieving DAS28 "low disease" (LDAS, <=3.2) at Wk24. Secondary effectiveness variables included ACR responses, CDAI, SDAI, inflammatory markers, and patient-reported outcomes such as HAQ-DI and FACIT-F (fatigue). Additional analyses considered several subgroups, e.g. based on rheumatoid factor (RF) at Baseline (RF+ vs. RF-), inadequate response (IR) to previous antirheumatics (TNFa-IR vs. cDMARD-IR), or Baseline DAS28 (>4.1-<=5.1 vs. >5.1).

Results:

286 pts. (ITT; median age: 55 yrs., 75.5% women, Baseline DAS28: 6.0±1.0) received TCZ; 239 pts. (71.6%) completed the 24wk treatment. 119 pts. (41.6%) had previously received TNFa-blockers; 163 (57.0%) cDMARDs only. 81 pts. (28.3%) were considered RF- and 184 pts. (64.3%) RF+. 47 pts. (16.4%) showed a Baseline DAS28 4.1-<=5.1 whilst 217 pts. (75.9%) had DAS28 >5.1.

At Wk24, 57% of the ITT pts. (95%-CI: [51.0; 62.8]) had achieved LDAS, ACR20/50/70 response rates were 65.0%/50.7%/33.9%. "Good" and "moderate" EULAR response was seen in 54.9% and 20.3% of pts., respectively. A clinically significant DAS28 reduction from Baseline (by >=1.2) was seen in 74.5% of pts.; 47.6% achieved DAS remission (<2.6). The mean course of continuous effectiveness variables is provided in Table 1 (relevant improvements were seen as early as Wk4).

Table 1. Results (continuous data) of the Week 24 effectiveness analyses (ITT, LOCF)

 Baseline mean ± SD (N obs.)Week 24/Early withdrawal mean ± SD (N obs.)Mean Change mean ± SD (N obs.)
Single variables   
SJC (n)9.6 ± 5.4 (286)2.6 ± 3.7 (286)-7.0 ± 5.5 (286)
TJC (n)12.6 ± 6.8 (286)4.3 ± 6.1 (286)-8.3 ± 6.6 (286)
VAS-Disease Activity (mm)62.2 ± 20.2 (286)26.3 ± 25.4 (286)-35.9 ± 30.2 (286)
ESR (mm/h)37.4 ± 22.1 (274)7.1 ± 9.5 (286)-30.3 ± 21.7 (274)
CRP (mg/L)23.1 ± 30.7 (274)3.0 ± 7.7 (286)-20.1 ± 29.9 (274)
Composite measures   
DAS286.0 ± 1.0 (274)2.6 ± 1.5 (286)-3.4 ± 1.4 (274)
CDAI34.7 ± 12.5 (284)11.3 ± 11.5 (285)-23.5 ± 13.3 (284)
SDAI37.2 ± 13.1 (272)11.6 ± 11.5 (285)-25.9 ± 13.7 (272)
Patient-reported outcome (PRO) measures   
HAQ-DI1.48 ± 0.65 (285)1.00 ± 0.75 (286)-0.48 ± 0.60 (285)
FACIT-F (fatigue)28.8 ± 11.2 (283)37.4 ± 12.2 (286)8.6 ± 11.1 (283)
N obs.=number of observations, SD=standard deviation.

The proportions of subgroup pts. achieving LDAS or DAS remission at Wk 24 are summarized in Table 2.

Table 2. LDAS and DAS28 remission in several subgroups at Week 24

Baseline CharacteristicsN (=100.0%)LDAS n (%)DAS28-Remission n (%)
Rheumatoid factor   
Positive184105 (57.1)85 (46.2)
Negative8148 (59.3)41 (50.6)
Previous RA treatment   
Conventional DMARD-IR163103 (63.2)87 (53.4)
TNFa-IR11960 (50.4)49 (41.2)
Baseline DAS28   
4.1 < DAS28 <=5.14734 (72.3)27 (57.4)
DAS28 >5.1217115 (53.0)95 (43.8)

Conclusions:

In a clinical setting close to usual care the treatment with TCZ led to rapid and sustained improvement of RA symptoms, thereby indicating the therapeutic benefits of TCZ. This improvement was consistently observed in all applied outcome measures independent of the measure characteristics. Subgroup analyses showed numerically better outcomes (i.e., difference by >10.0 percentage points in both LDAS and DAS remission when compared with the complementary group) in cDMARD-IR vs. TNFa-IR pts. or pts. with baseline DAS28 4.1-<=5.1 vs. >5.1, whereas no such differences were seen between RF+ vs. RF- pts., thereby suggesting that RF seemed not to relevantly predict the outcome at Wk 24.

To cite this abstract, please use the following information:
Feist, Eugen, Rubbert-Roth, Andrea, Braun, Jürgen, Kaufmann, Jörg, Kellner, Herbert L., Kurthen, Reiner, et al; A Study To Evaluate the Effectiveness and Safety of the Interleukin-6 (IL-6) Receptor Antagonist Tocilizumab (TCZ) after 4 and 24 Weeks in Patients with Active Rheumatoid Arthritis (RA)Final Effectiveness Results of the TAMARA Study. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1788
DOI: 10.1002/art.29553

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